This project will continue on-going experimental behavioral pharmacology studies of methadone self-administration by methadone-dependent human volunteers. The project aims to identify and study factors influencing opoid (methadone) self-administration and facilitating the reduction of opioid self-administration. In a residential human experimental laboratory volunteer methadone patients are allowed significant self-control over the amount and pattern of their oral methadone ingestion. We will explore experimentally both behavioral and pharmacological factors influencing the probability of opiod self-administration. One group of studies will examine a series of pharmacological treatments thought to influence methadone self-administration and/or methadone detoxification. We will examine the effects of clonidine and one of the benzodiazepine minor tranquilizers; in addition, we will evaluate the ability of these adjunct medications to maintain self-administration in their own right during methadone detoxification. Also, we will evaluate the effects of pretreatment with morphine or with the narcotic antagonist naloxone upon methadone self-administration. A second group of studies will evaluate the relevance as determinants of methadone self-administration of three of the major behavioral conceptualizations concerning factors presumed to influence drug self-administration - the scheduled social environment consequences of the behavior; the extent of reinforcement of alternative behaviors; and exposure to drug-related stimuli presumed to elicit a conditioned craving. In all studies measures of the amount and pattern of voluntary methadone self-administration constitute the data of primary interest. In addition, detailed concurrent assessments of patients' subjective, psychophysiological and behavioral status will be made. These experiments will provide multifaceted data concerning environmental and pharmacological influence upon human opioid self-administration, and concerning the characteristics and correlates of chronic opioid self-administration and of drug dependence in general.